Diabetes and Iron Transport

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Type 1 diabetes is partly inherited, and then triggered by certain infections. Type 2 diabetes is due primarily to lifestyle factors and genetics. Scientists have been trying to explain the multiple causes of diabetes for many years. Researchers at the University of Copenhagen and Novo Nordisk A/S have now shown that the increased activity of one particular iron-transport protein destroys insulin-producing beta cells. In addition, the new research shows that mice without this iron transporter are protected against developing diabetes. These results have just been published in the prestigious journal Cell Metabolism.

Type 1 diabetes is partly inherited, and then triggered by certain
infections. Type 2 diabetes is due primarily to lifestyle factors and
genetics. Scientists have been trying to explain the multiple causes of
diabetes for many years. Researchers at the University of Copenhagen
and Novo Nordisk A/S have now shown that the increased activity of one
particular iron-transport protein destroys insulin-producing beta cells.
In addition, the new research shows that mice without this iron
transporter are protected against developing diabetes. These results
have just been published in the prestigious journal Cell Metabolism.

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Almost 300,000 in Denmark have diabetes â€” 80 per cent have type-2
diabetes, a so-called lifestyle disease. The number of people with
diabetes doubles every decade. This is the case for many nations.

People
develop diabetes when the beta cells in their pancreas do not produce
enough insulin to meet their body's needs. Beta cells store and release
insulin, a hormone that controls the level of glucose in the blood. The
liver maintains the base-line glucose level, but the beta cells can
respond quickly to spikes in blood glucose by releasing some of its
stored insulin while simultaneously producing more. The response time is
very quick.

New research from the University of Copenhagen and
Novo Nordisk A/S links this defect to one particular cellular iron
transporter: "Iron is a vital mineral for the healthy functioning of the
body and is found in many enzymes and proteins, for example, the red
blood pigment that transports oxygen. But iron can also promote the
creation of toxic oxygen radicals. An increase in the iron content of
the cells may cause tissue damage and disease. We find that increased
activity of a certain iron transporter causes damage to the beta cell.
And if we completely remove this iron transporter in the beta cells in
genetically engineered mice, they are indeed protected against
diabetes," explains Professor Thomas Mandrup-Poulsen, Department of
Biomedical Sciences, The Faculty of Health and Medical Sciences.

The
University of Copenhagen researchers have previously documented a
connection between surplus iron and diabetes risk, based on large
population studies. But this is the first time that scientists have
found a link between inflammation and iron transport, which appears to
be the underlying cause of the observed higher risk:

"We need to
conduct controlled clinical trials showing that changes in the iron
content of the body can reduce the risk of diabetes. Only then will we
be able to advise people at risk of diabetes not to take iron
supplements, or recommend drug treatment to reduce the amount of iron in
the body," says Thomas Mandrup-Poulsen.

The team behind the
scientific article in Cell Metabolism can see that the inflammatory
signal substances created around the beta cells in both type-1 and
type-2 diabetes accelerate the activity of the iron transporter. "The
evolutionary explanation of why the highly specialised beta cells are
influenced by the inflammatory signal substances and contain the
potentially dangerous iron transport proteins is presumably that the
short-term increase in the amount of oxygen radicals is critical to the
fine-tuning of insulin production during bouts of fever and stress.
However, nature had not foreseen the long-term local production of
signal substances around the beta cells, which we see in type-1 and
type-2 diabetes," continues Thomas Mandrup-Poulsen.